This project describes our goals in identifying and studying mechanisms of suppression during infection with intracellular pathogenic microorganisms. We want to study murine infection with Listeria monocytogenes because, first, this is a well-studied infection in the mouse in which specific resistance is known to depend on T cell activation of macrophages; and, second, our past work, which has led us to develop a number of assays for studying various stages of macrophage-T cell interactions. This proposal is divided into two complementary projects. The first studies a model of transitory and severe susceptibility to infection caused by acute formation of immune complexes. Mice immunized to a protein become highly susceptible to Listeria infection when challenged with the protein antigen: most mice that receive about one-tenth of the LD50 dose die with ten thousand to a million more bacteria in tissues, unaccompanied by the normal granulomatous response. A paucity of Ia-positive macrophages is also found. This phenomenon can be transferred to normal mice by affinity-purified antibodies. Our immediate goals are to identify which Ig class is responsible, define the possible role of complement and T suppressor cells, determine if anaphylactic antibodies are participating, and to assess the importance of natural resistance mechanisms. We expect to be able to define the mechanisms by which immune complexes lead to suppression and the cellular level at which they act (i.e., macrophages, T helper cells, etc.). We will assess in culture those processes that may be relevant to the in vivo effect. A second project studies the role of T suppressor cells in modulating immunity to Listeria and considers three approaches for inducing these cells. These involve infecting with high dose of Listeria (then curing the infection), giving Listeria products or heat-killed organisms, or administering antibodies to I-region gene products. T suppressors will be tested in vivo and also in culture. Our purpose will be to define how T suppressor cells affect the interactions between macrophages and T helper cells. Attempts will be made to define what form of antigen will the T suppressor cells recognize (Listeria that is macrophage associated?; or macrophage processed?; or free?), whether soluble factors affect the macrophage in its antigen presentation and/or whether T helper cells are directly affected. In this well-characterized murine infection, we plan to define mechanisms of suppression relevant to human infection.